Pharmacokinetics, Pharmacodynamics and Preliminary Observations for Clinical Activity and Safety of Multiple Doses of Human Mouse Chimeric Anti-CD22 Monoclonal Antibody (SM03) in Chinese Patients with Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVES

SM03 is a novel recombinant, human/mouse chimeric immunoglobulin G1 monoclonal antibody directed against the CD22 antigen on human B lymphocytes. This was the first study to investigate the pharmacokinetics, pharmacodynamics, immunogenicity, safety and clinical activity of SM03 in patients with systemic lupus erythematosus (SLE).

METHODS

This study was an open, multiple-centre, parallel-group, multiple-ascending-dose, phase I study in 29 SLE patients. Pharmacokinetic assessment was conducted in 22 of these patients. Eligible patients received multiple intravenous infusions of SM03 for 4 weeks (240 mg/m, 600 or 900 mg, once weekly) and were monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety and clinical response.

RESULTS

After multiple-dose SM03, the maximal serum concentration of SM03 was reached within 3-7 h. The mean elimination half-life was 15 days. The average accumulation ratios of the area under the time-concentration curve and the maximum concentration after the fourth administration of SM03 were 2.0 and 1.5. CD19 B-lymphocyte counts were decreased. Infections were the most common adverse events. No drug-related serious adverse events were reported. The therapeutic benefit of SM03 was observed mainly in patients with moderate-to-severe disease activity.

CONCLUSION

Pharmacokinetic exposure increased in a lower-than-dose-proportional manner up to 900 mg. SM03 was well tolerated at doses ranging from 240 mg/m to 900 mg, with no new safety signals identified. SM03 has potential efficacy in Chinese patients with SLE.